This research project is designed to determine the mechanisms by which gonococci cause disease in the human genital tract. Most phases of these studies use an experimental model of human fallopian tubes in organ culture in which the rate of damage to the human genital mucosa by gonococci can be quantitated and the interaction of gonococci with human genital mucosa can be studied by light electron microscopy. This model is being used to study factors, such as pili, that influence attachment to human genital mucosa. Investigations in this laboratory have demonstrated that gonococci elaborate a toxic factor which damages human genital mucosa. In the proposed work studies will be performed to determine the nature of this toxic factor or factors and ways to interfere with its toxic action. Studies performed in this laboratory also suggest that gonococci are phagocytized by mucus-secreting cells of the fallopian tube mucosa and eventually make their way to the submucosa. We plan to study this phenomenon in greater detail to see if this is a likely route for dissemination of gonococcal infections and if so, how it can be interferred with. As indicated, the goal of these studies is to develop more effective means of preventing gonococcal infections.